MicroRNA hsa-miR-29 与多种恶性肿瘤有关。其靶基因很多，其中Mcl-1以三种可能的亚型表达，其中一种是抗凋亡的，另一种是促凋亡的。这两种亚型的比例似乎会影响细胞对外部刺激的反应。我们已经证明，miR-29b 通过调节 Mcl-1 异构体的比例来增强 HeLa 细胞系中依托泊苷的毒性。然而，目前尚不清楚所描述的 miR-29 效应是否对各种癌症类型都有共同作用，甚至是否具有相反的作用。这对于未来可能的应用来说是一个重大问题。在本报告中，我们证明 miR-29b 会影响 60 μM 依托泊苷在源自选定恶性肿瘤的细胞系中的毒性。然而，所测试的细胞系之间的机制有所不同。 Hep G2 细胞表现出 miR-29b 对依托泊苷毒性的影响与 HeLa 细胞中描述的类似，即调节 Mcl-1 表达。然而，被 miR-29b 下调导致 Caco-2 细胞中依托泊苷毒性增强的靶蛋白是 Bcl-2 蛋白。此外，被选为非恶性细胞代表的H9c2、Hek-293和ARPE-19细胞系显示miR-29b对依托泊苷毒性没有影响。我们的数据表明，由于 miR-29b 对 Bcl 家族蛋白的调节，miR-29b 可能是恶性细胞中依托泊苷毒性的常见增强剂。© 2024。作者。

MicroRNA hsa-miR-29 was connected to a number of malignancies. Its target genes are many, among them Mcl-1 that is expressed in three possible isoforms, one of which is anti-apoptotic and another one pro-apoptotic. Ratio of these two isoforms appears to affect cell response to external stimuli. We have demonstrated that miR-29b enhanced etoposide toxicity in HeLa cell line by modulating this ratio of Mcl-1 isoforms. However, it is not known whether the described miR-29 effect is common to various cancer types or even have the opposite effect. This represents a significant problem for possible future applications. In this report, we demonstrate that miR-29b affects toxicity of 60 μM etoposide in cell lines derived from selected malignancies. The mechanism, however, differs among the cell lines tested. Hep G2 cells demonstrated similar effect of miR-29b on etoposide toxicity as was described in HeLa cells, i.e. modulation of Mcl-1 expression. Target protein down-regulated by miR-29b resulting in enhanced etoposide toxicity in Caco-2 cells was, however, Bcl-2 protein. Moreover, H9c2, Hek-293 and ARPE-19 cell lines selected as a representatives of non-malignant cells, showed no effect of miR-29b on etoposide toxicity. Our data suggest that miR-29b could be a common enhancer of etoposide toxicity in malignant cells due to its modulation of Bcl family proteins.© 2024. The Author(s).